Trisha E Wong1, Thuan Nguyen, Samir S Shah, Thomas V Brogan, Char M Witmer. 1. 1Division of Hematology/Oncology, Departments of Pediatrics and Pathology, Oregon Health and Science University, Portland, OR.2Department of Public Health & Preventive Medicine, Biostatistics & Design Program, Oregon Health and Science University, Portland, OR.3Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.4Division of Critical Care, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.5Division of Hematology, Department of Pediatrics, The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Abstract
OBJECTIVE: To describe antithrombin concentrate use and to compare thrombotic and hemorrhagic outcomes throughout the hospital stay in pediatric subjects who received extracorporeal membrane oxygenation in a Pediatric Health Information System-participating children's hospital. DESIGN: Retrospective, multi-center, cohort study. SETTING: Forty-three free-standing children's hospitals participating in Pediatric Health Information System. SUBJECTS: Children older than or equal to 18 years of age who underwent extracorporeal membrane oxygenation between 2003 and 2012. INTERVENTIONS: Subjects were classified as receiving antithrombin if they received at least one dose of antithrombin while on extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: International Classification of Diseases, Ninth Revision, Clinical Modification codes codes were used to identify hemorrhagic and thrombotic complications during their hospitalization. Pediatric Health Information System data were analyzed to determine hospital-length of stay and in-hospital mortality. A total of 1,931 of 8,601 eligible subjects (21.5%) received at least one dose of antithrombin during their extracorporeal membrane oxygenation course. Antithrombin use during extracorporeal membrane oxygenation increased from 2.4% to 51.9% (p < 0.001) over the 10-year study period. Subjects who received antithrombin while on extracorporeal membrane oxygenation were younger (p = 0.02), had more chronic conditions (p < 0.001), and longer hospital stays (p < 0.001). On multivariate analysis, antithrombin use was associated with thrombotic events (odds ratio, 1.55; 95% CI, 1.36-1.77; p < 0.001), hemorrhagic events (odds ratio, 1.27; 95% CI, 1.14-1.42; p < 0.001), and longer hospital length of stays (slope coefficient, 1.05 d; 95% CI, 1.04-1.06; p < 0.001). No difference was observed in mortality (odds ratio, 0.99; 95% CI, 0.89-1.11; p = 0.90). CONCLUSIONS: In this multicenter retrospective cohort study, subjects who received antithrombin during extracorporeal membrane oxygenation had a higher number of thrombotic and hemorrhagic events throughout the hospitalization and longer length of stays without an associated difference in mortality. While limitations exist with this analysis and results should be interpreted with caution, the fact remains that over half of pediatric patients on extracorporeal membrane oxygenation are currently receiving antithrombin without clear benefit, with extra cost, and potential harms, there needs to be strong consideration for a clinical trial.
OBJECTIVE: To describe antithrombin concentrate use and to compare thrombotic and hemorrhagic outcomes throughout the hospital stay in pediatric subjects who received extracorporeal membrane oxygenation in a Pediatric Health Information System-participating children's hospital. DESIGN: Retrospective, multi-center, cohort study. SETTING: Forty-three free-standing children's hospitals participating in Pediatric Health Information System. SUBJECTS:Children older than or equal to 18 years of age who underwent extracorporeal membrane oxygenation between 2003 and 2012. INTERVENTIONS: Subjects were classified as receiving antithrombin if they received at least one dose of antithrombin while on extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: International Classification of Diseases, Ninth Revision, Clinical Modification codes codes were used to identify hemorrhagic and thrombotic complications during their hospitalization. Pediatric Health Information System data were analyzed to determine hospital-length of stay and in-hospital mortality. A total of 1,931 of 8,601 eligible subjects (21.5%) received at least one dose of antithrombin during their extracorporeal membrane oxygenation course. Antithrombin use during extracorporeal membrane oxygenation increased from 2.4% to 51.9% (p < 0.001) over the 10-year study period. Subjects who received antithrombin while on extracorporeal membrane oxygenation were younger (p = 0.02), had more chronic conditions (p < 0.001), and longer hospital stays (p < 0.001). On multivariate analysis, antithrombin use was associated with thrombotic events (odds ratio, 1.55; 95% CI, 1.36-1.77; p < 0.001), hemorrhagic events (odds ratio, 1.27; 95% CI, 1.14-1.42; p < 0.001), and longer hospital length of stays (slope coefficient, 1.05 d; 95% CI, 1.04-1.06; p < 0.001). No difference was observed in mortality (odds ratio, 0.99; 95% CI, 0.89-1.11; p = 0.90). CONCLUSIONS: In this multicenter retrospective cohort study, subjects who received antithrombin during extracorporeal membrane oxygenation had a higher number of thrombotic and hemorrhagic events throughout the hospitalization and longer length of stays without an associated difference in mortality. While limitations exist with this analysis and results should be interpreted with caution, the fact remains that over half of pediatric patients on extracorporeal membrane oxygenation are currently receiving antithrombin without clear benefit, with extra cost, and potential harms, there needs to be strong consideration for a clinical trial.